Characterizing interactions of Leptospira interrogans with proximal renal tubule epithelial cells
Abstract Background Leptospira interrogans is a pathogenic, spirochetal bacterium that is responsible for leptospirosis, an emerging worldwide zoonosis. Leptospires colonize the renal proximal tubules and chronically infect the kidney. Live bacteria are excreted into urine, contaminating the environ...
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | BMC Microbiology |
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| Online Access: | http://link.springer.com/article/10.1186/s12866-018-1206-8 |
| _version_ | 1819238605380386816 |
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| author | Takayoshi Yamaguchi Naomi Higa Nobuhiko Okura Arina Matsumoto Idam Hermawan Tetsu Yamashiro Toshihiko Suzuki Claudia Toma |
| author_facet | Takayoshi Yamaguchi Naomi Higa Nobuhiko Okura Arina Matsumoto Idam Hermawan Tetsu Yamashiro Toshihiko Suzuki Claudia Toma |
| author_sort | Takayoshi Yamaguchi |
| collection | DOAJ |
| description | Abstract Background Leptospira interrogans is a pathogenic, spirochetal bacterium that is responsible for leptospirosis, an emerging worldwide zoonosis. Leptospires colonize the renal proximal tubules and chronically infect the kidney. Live bacteria are excreted into urine, contaminating the environment. While it is well known that leptospires can persist in the kidneys without signs of disease for several months, the interactions of leptospires with the proximal renal epithelial tubule cells that allow the chronic renal colonization have not been elucidated yet. In the present study, we compared the interactions between a virulent, low passage (LP) strain and a cultured-attenuated, high passage (HP) strain with renal proximal tubule epithelial cells (RPTECs) to elucidate the strategies used by Leptospira to colonize the kidney. Results Kinetics analysis of kidney colonization in a mouse model of chronic infection performed by quantitative real-time PCR and immunofluorescence, showed that the LP strain reached the kidney by 3 days post infection (pi) and attached to the basal membrane side of the renal epithelial cells. At 10 days pi, some leptospires were attached to the luminal side of the tubular epithelia and the number of colonizing leptospires gradually increased. On the other hand, the HP strain was cleared during hematogenous dissemination and did not colonize the kidney. Transmission electron microscopy analysis of LP-infected kidneys at 25 days pi showed aggregated leptospires and membrane vesicles attached to the epithelial brush border. Leptospiral kidney colonization altered the organization of the RPTEC brush border. An in vitro model of infection using TCMK-1 cells, showed that leptospiral infection induced a host stress response, which is delayed in LP-infected cells. Conclusions After hematogenous dissemination, leptospires create protective and replicative niches in the base membrane and luminal sides of the RPTECs. During the long-term colonization, leptospires attached to the RPTEC brush borders and membrane vesicles might be involved in the formation of a biofilm-like structure in vivo. Our results also suggested that the virulent strain is able to manipulate host cell stress responses to promote renal colonization. |
| first_indexed | 2024-12-23T13:38:53Z |
| format | Article |
| id | doaj.art-a51debedc56f40beb93d2476a512cd76 |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-12-23T13:38:53Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
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| series | BMC Microbiology |
| spelling | doaj.art-a51debedc56f40beb93d2476a512cd762022-12-21T17:44:55ZengBMCBMC Microbiology1471-21802018-07-0118111110.1186/s12866-018-1206-8Characterizing interactions of Leptospira interrogans with proximal renal tubule epithelial cellsTakayoshi Yamaguchi0Naomi Higa1Nobuhiko Okura2Arina Matsumoto3Idam Hermawan4Tetsu Yamashiro5Toshihiko Suzuki6Claudia Toma7Department of Bacteriology, Graduate School of Medicine, University of the RyukyusDepartment of Bacteriology, Graduate School of Medicine, University of the RyukyusDepartment of Molecular Anatomy, Graduate School of Medicine, University of the RyukyusDepartment of Bacteriology, Graduate School of Medicine, University of the RyukyusDepartment of Bacteriology, Graduate School of Medicine, University of the RyukyusDepartment of Bacteriology, Graduate School of Medicine, University of the RyukyusDepartment of Bacterial Pathogenesis, Infection and Host Response, Graduate School of Medicine and Dental Sciences, Tokyo Medical and Dental UniversityDepartment of Bacteriology, Graduate School of Medicine, University of the RyukyusAbstract Background Leptospira interrogans is a pathogenic, spirochetal bacterium that is responsible for leptospirosis, an emerging worldwide zoonosis. Leptospires colonize the renal proximal tubules and chronically infect the kidney. Live bacteria are excreted into urine, contaminating the environment. While it is well known that leptospires can persist in the kidneys without signs of disease for several months, the interactions of leptospires with the proximal renal epithelial tubule cells that allow the chronic renal colonization have not been elucidated yet. In the present study, we compared the interactions between a virulent, low passage (LP) strain and a cultured-attenuated, high passage (HP) strain with renal proximal tubule epithelial cells (RPTECs) to elucidate the strategies used by Leptospira to colonize the kidney. Results Kinetics analysis of kidney colonization in a mouse model of chronic infection performed by quantitative real-time PCR and immunofluorescence, showed that the LP strain reached the kidney by 3 days post infection (pi) and attached to the basal membrane side of the renal epithelial cells. At 10 days pi, some leptospires were attached to the luminal side of the tubular epithelia and the number of colonizing leptospires gradually increased. On the other hand, the HP strain was cleared during hematogenous dissemination and did not colonize the kidney. Transmission electron microscopy analysis of LP-infected kidneys at 25 days pi showed aggregated leptospires and membrane vesicles attached to the epithelial brush border. Leptospiral kidney colonization altered the organization of the RPTEC brush border. An in vitro model of infection using TCMK-1 cells, showed that leptospiral infection induced a host stress response, which is delayed in LP-infected cells. Conclusions After hematogenous dissemination, leptospires create protective and replicative niches in the base membrane and luminal sides of the RPTECs. During the long-term colonization, leptospires attached to the RPTEC brush borders and membrane vesicles might be involved in the formation of a biofilm-like structure in vivo. Our results also suggested that the virulent strain is able to manipulate host cell stress responses to promote renal colonization.http://link.springer.com/article/10.1186/s12866-018-1206-8Leptospira interrogansKidneyColonizationProximal tubuleRenal epithelial cell |
| spellingShingle | Takayoshi Yamaguchi Naomi Higa Nobuhiko Okura Arina Matsumoto Idam Hermawan Tetsu Yamashiro Toshihiko Suzuki Claudia Toma Characterizing interactions of Leptospira interrogans with proximal renal tubule epithelial cells BMC Microbiology Leptospira interrogans Kidney Colonization Proximal tubule Renal epithelial cell |
| title | Characterizing interactions of Leptospira interrogans with proximal renal tubule epithelial cells |
| title_full | Characterizing interactions of Leptospira interrogans with proximal renal tubule epithelial cells |
| title_fullStr | Characterizing interactions of Leptospira interrogans with proximal renal tubule epithelial cells |
| title_full_unstemmed | Characterizing interactions of Leptospira interrogans with proximal renal tubule epithelial cells |
| title_short | Characterizing interactions of Leptospira interrogans with proximal renal tubule epithelial cells |
| title_sort | characterizing interactions of leptospira interrogans with proximal renal tubule epithelial cells |
| topic | Leptospira interrogans Kidney Colonization Proximal tubule Renal epithelial cell |
| url | http://link.springer.com/article/10.1186/s12866-018-1206-8 |
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